Intrathecal administration of a new nitric oxide donor, NOC-18, produces acute thermal hyperalgesia in the rat.
A nitric oxide releasing compound, NOC-18, was injected intrathecally in order to determine the role of NO in spinal nociceptive mechanisms in rats. The nociceptive threshold was evaluated by the radiant heat tail-flick test. The effects of intrathecal injection of N-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor; methylene blue (MB), a soluble guanylate cyclase inhibitor and hemoglobin (Hb), an NO scavenger, on the nociceptive threshold were measured in the presence and absence of 0.1, 1 and 10 microg of NOC-18. The results were compared with a control group of rats which were injected with the same volume of normal saline. NOC-18 caused a dose-dependent curtailment of the tail-flick latency during the period from 15 to 150 min. L-NAME, MB and Hb all produced prolongation of the tail-flick latency during the same time period. The hyperalgesia induced by this concentration range of NOC-18 was completely blocked by Hb, but was not affected by either L-NAME or MB. These findings indicate that NO plays a direct role in thermal hyperalgesia in the spinal cord, and that an another pathway in addition to the NO-cGMP pathway may be involved.
Inoue
T
T
Department of Anesthesiology, Osaka University Medical School, Suita City, Japan.
Mashimo
T
T
Shibuta
S
S
Yoshiya
I
I
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006454:Hemoglobins / Q000494:pharmacology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced* / Q000523:psychology; D007278:Injections, Spinal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009603:Nitroso Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
D004791:Enzyme Inhibitors; D006454:Hemoglobins; C093285:NOC 18; D009603:Nitroso Compounds; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D019331:NG-Nitroarginine Methyl Ester